Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

Abstract

Context: Acetylshikonin, a naphthoquinone derivative, is mainly extracted from some species of the family Boraginaceae, such as Lithospermum erythrorhizon Sieb. et Zucc., Arnebia euchroma (Royle) Johnst., and Arnebia guttata Bunge. As a bioactive compound, acetylshikonin has attracted much attention because of its broad pharmacological properties. Objective: This review provides a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of acetylshikonin focussing on its mechanisms on the basis of currently available literature. Methods: The information of acetylshikonin from 1977 to 2020 was collected using major databases including Elsevier, Scholar, PubMed, Springer, Web of Science, and CNKI. Acetylshikonin, pharmacology, toxicity, pharmacokinetics, and naphthoquinone derivative were used as key words. Results: According to emerging evidence, acetylshikonin exerts a wide spectrum of pharmacological effects such as anticancer, anti-inflammatory, lipid-regulatory, antidiabetic, antibacterial, antifungal, antioxidative, neuroprotective, and antiviral properties. However, only a few studies have reported the adverse effects of acetylshikonin, with respect to reproductive toxicity and genotoxicity. Pharmacokinetic studies demonstrate that acetylshikonin is associated with a wide distribution and poor absorption. Conclusions: Although experimental data supports the beneficial effects of this compound, acetylshikonin cannot be considered as a therapy drug without further investigations, especially, on the toxicity and pharmacokinetics.

Shikonin derivatives cause apoptosis and cell cycle arrest in human chondrosarcoma cells via death receptors and MAPK regulation

“…Known mechanisms of action are the inhibition of cell proliferation, induction of apoptosis, and reduction of cell migration and invasion potential through a variety of molecular signal transduction pathways [ 12 , 13 ]. Acetylshikonin, another promising naturally occurring shikonin derivative, have also several pharmacological effects [ 14 ]. In addition, attempts have been made to optimize antitumorigenic activity by modulating the structure of naturally occurring shikonin derivatives.…”

Shikonin Derivatives Inhibit Inflammation Processes and Modulate MAPK Signaling in Human Healthy and Osteoarthritis Chondrocytes

“…To study the effects of shikonin and its derivatives ( Figure 1 A) in healthy chondrocytes (HC) and primary OA chondrocytes (pCH-OA), cells were treated with various concentrations of the compounds of interest, and the dose-response relationship was analyzed. Shikonin and acetylshikonin are naturally occurring shikonin derivatives [ 15 , 16 , 17 ]. Cyclopropylshikonin was synthesized in a previous study and found to be the most cytotoxic compound out of a screening of novel shikonin derivatives [ 18 ].…”

“…The mechanisms of action included, for example, inhibition of cell proliferation, induction of apoptosis, and reduced cell migration and invasion through a variety of molecular signal transduction pathways. Another promising, naturally occurring shikonin derivative is acetylshikonin, which has also been reported to possess several pharmacological activities [ 15 , 16 , 17 ]. Furthermore, several attempts have been made to optimize the naturally occurring shikonin derivatives by modulating the structure.…”

Anticancer Mechanism of the Non-polar Extract from Echium angustifolium Mill. Aerial Parts in Relation to Its Chemical Content

“…Trolox equivalent antioxidant capacity was determined, which yielded values of 131.05 and 1407.24 μM TE/ mg extract using DPPH and ABTS tests, respectively (Table 2). This extract was proven to include a number of well-known antioxidants, including cinnamic acid derivatives [29], and acetylshikonin [30]. Despite this, antagonism between substances in the plant mixture could explain the mild effect [31].…”